At a most fundamental level, complex biological systems emerge from the interplay of proteins, nucleic acids, other types of macromolecules and small molecule compounds. To understand the details of these interactions, an increasing number of health-related researchers are turning to X-ray crystallography, a technique that is generally applicable for determining the atomic-resolution structures of complex biological macromolecules independent of size. These structures are then used to guide our understanding of related biological properties and functions. In order to continue to provide state-of-the-art crystallographic instrumentation and resources to our local community of scientists, this proposal seeks funding to upgrade components of our shared crystallographic facilities. The best of our existing generators and data collection devices will be reconfigured with new instrumentation to increase dramatically both the quality as well as the quantity of collected diffraction data. These enhanced capacities will serve our community well as we advance into new areas of structural proteomics, chemical biology and associated quantitative structure-activity relationships, and the structure determination of ever larger protein complexes including membrane proteins. [unreadable] The Biomolecular X-ray Crystallography Core at the University of North Carolina at Chapel Hill supports the studies of numerous health-related scientists. These researchers are interested in various diverse biological processes. For example, some researchers are interested in the intrinsic and chaperone-mediated folding and stability of individual proteins. Other researchers study the formation of large and dynamic complexes that facilitate and regulate the capacity of cells to sense their external environment and respond appropriately. A fundamental tenant of macromolecular X-ray crystallography is that by understanding the structures of individual macromolecules as well as large protein complexes, we will be better able to understand and treat the complex biological systems that emerge from these fundamental components. In this way, macromolecular X-ray crystallography guides our detailed understanding of human biology and provides essential avenues for new drug treatments [unreadable] [unreadable] [unreadable] [unreadable]